Genetic basis of Hereditary nephritis in Samoyeds - also known as Samoyed Hereditary Glomerulopathy (SHG), is caused by a nonsense mutation in the COL4A5 gene, located on the X chromosome. This mutation leads to a premature stop codon in the gene, resulting in approximately 90% reduction of type IV collagen production, essential for the structural integrity of the glomerular basement membrane in kidneys. The disease is inherited in an X-linked dominant pattern, which means males (having one X chromosome) are more severely affected, while females (with two X chromosomes) are typically carriers with milder or later-onset symptoms. This COL4A5 gene mutation and resulting condition in Samoyeds is a canine model for human Alport Syndrome, which also involves mutations in COL4A3, COL4A4, and COL4A5 genes affecting basement membrane collagen.
Pathophysiology - The COL4A5 gene mutation disrupts the synthesis of type IV collagen, a key component of basement membranes in the kidney glomerulus, inner ear, and eye. This disruption causes abnormal glomerular basement membranes, leading to progressive damage of the kidney filters and eventual kidney failure. Proteinuria (excess protein in urine) appears early, around 3–4 months of age. In affected males, severe kidney damage progresses rapidly, causing kidney failure typically by 8 to 15 months of age. Female carriers may develop slower progression of kidney disease due to mosaic expression of the mutated gene. Hearing loss and other systemic symptoms commonly found in human Alport syndrome are less consistently reported in Samoyeds but the kidney pathology is similar.
Complications - Progressive kidney failure in affected dogs, with clinical signs of proteinuria, kidney dysfunction, and ultimately death. Male Samoyeds usually succumb by 1–1.5 years of age without intervention. Kidney disease progression in females is variable and typically slower. The condition is fatal if untreated and leads to end-stage renal disease. Early signs include protein loss in urine; later signs include uremia and systemic illness from kidney failure.
Why This Matters to Breeders and Vets - Breeders must be aware of the genetic nature and inheritance pattern to avoid producing affected males and limit disease incidence. Genetic testing is available for the COL4A5 mutation to identify carriers and affected dogs. Veterinarians should recognize early signs like proteinuria, especially in young Samoyeds, to permit early diagnosis and possible therapeutic intervention. Understanding the disease helps differentiate hereditary nephritis from other renal diseases in dogs and supports counseling of owners regarding prognosis and breeding decisions.
Summary - Alport Syndrome or Hereditary Nephritis (Samoyed Type) is an X-linked dominant inherited kidney disease caused by a nonsense mutation in the COL4A5 gene, leading to deficient type IV collagen in the glomerular basement membrane. This causes early-onset, progressively fatal kidney disease primarily in male Samoyeds, with milder effects in females. Genetic testing facilitates diagnosis and breeding decisions to prevent affected puppies and improve breed health management.